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Parkinsonian-pyramidal syndrome (MONDO:0009830) features combined parkinsonism and pyramidal signs. SNCA (SNCA) encodes alpha-synuclein, an autosomal dominant Parkinson disease gene associated with Lewy body pathology.
In a cohort of 39 indigenous Zambian patients, including one with parkinsonian-pyramidal syndrome, comprehensive SNCA exon sequencing in the syndromic case revealed no pathogenic SNCA coding variants (PMID:22445250). No familial segregation or additional affected relatives with SNCA variants were reported.
Although extensive functional studies demonstrate that PD-linked SNCA mutations accelerate alpha-synuclein fibril formation and disrupt neuronal proteostasis, no disease-specific functional or experimental data support a role for SNCA in parkinsonian-pyramidal syndrome. Given the lack of genetic and functional evidence, routine SNCA testing is not recommended for isolated parkinsonian-pyramidal presentations.
Key Take-home: SNCA involvement in parkinsonian-pyramidal syndrome remains unsubstantiated; evaluate SNCA primarily in established familial Parkinson disease contexts.
Gene–Disease AssociationLimitedSingle parkinsonian-pyramidal syndrome proband sequenced with no SNCA variants detected ([PMID:22445250]) Genetic EvidenceLimitedAbsence of SNCA coding variants in one syndromic case ([PMID:22445250]) Functional EvidenceLimitedPD-linked SNCA functional assays exist but lack disease-specific data for parkinsonian-pyramidal syndrome |